The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Computational modelling to optimize the hybrid configuration for hypoplastic left heart syndrome

Hybrid palliation for hypoplastic left heart syndrome (HLHS) is associated with mortality and late ventricular dysfunction. Increased ventricular workload and coronary perfusion limitation may be the important factors. Using mathematical modelling, this study investigated the effects of differing hybrid configurations on the demands on this single ventricle circulation. A multicompartmental Windkessel model of hybrid HLH-aortic atresia circulation was adopted, with a time-varying elastance representing ventricular functionality. The effects of diameter increases in bilateral pulmonary artery bandings (PABs) (+0.5, 2.5-4 mm) and ductal stent (+1, 4-10 mm) on cardiovascular haemodynamics, systemic oxygenation and ventricular energetics were assessed. Simulations showed that an increase in PAB diameter of 2.5-4 mm resulted in an increased Q (0.61-2.66), and diastolic stent backflow (-0.2 to -0.78 l/min) with reduced systemic perfusion (0.82-0.77 l/min) and diastolic pressures (48.3-41.2 mmHg). Arterial and venous saturations increased, SaO2 (%) was 62-88 and SvO(2) 41-65. To maintain mean systemic pressures, substantial increases in cardiac output (1.3-2.8 l/min) and ventricular stroke work (576-1360 mmHg ml) were required. A decrease in the ductal stent diameter over the range 10-7 mm had a negligible haemodynamic effect: reduced systemic systolic pressure (77-72 mmHg) and increase in ventricular stroke work (781-790 mmHg ml). When the ductal diameter was restricted to <7 mm, it resulted in a significant reduced systemic flow and increased stroke work. Optimal hybrid configuration was defined at PAB 3 mm and ductal stent ≥7 mm. In this model, increasing the PAB diameter, or a stent diameter <7 mm, substantially increased single ventricle workload and reduced systemic perfusion and diastolic pressure. This may compromise myocardial oxygen demand-supply, particularly in the setting of retrograde-dependent coronary perfusion

Place, memory and identity: Imagining 'New Asia'

10.1111/j.1467-8373.2005.00286.xAsia Pacific Viewpoint463247-25